ViiV DOVATO


Full Prescribing Information including Boxed Warning

Update Your Coverage Policy and Formulary to Include Your Members With HIV-1 Who Are Either Treatment-Naïve or Virologically Suppressed

DOVATO is now indicated for your members with HIV-1 who are either treatment-naïve or virologically suppressed.

DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable ARV regimen with no history of treatment failure and no known resistance to any component of DOVATO.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.

Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Please see additional Important Safety Information for DOVATO below.

For your virologically suppressed members with HIV-1

Offer Fewer ARVs With DOVATO, a Single-Tablet, 2-Drug Regimen

DOVATO Maintained Virologic Suppression at 48 Weeks as Effectively as TAF-Containing Regimens of 3 or More Drugs

Patients who switched to DOVATO had no increased rate of virologic failure vs those who remained on TAF-containing* regimens

TANGO—Noninferior Virologic Response (ITT–E; snapshot analysis)


*TAF/FTC + EVG/c, DTG, RAL, RPV, NPV, EFV, bATV, or bDRV.
4% noninferiority margin for primary endpoint; –8% noninferiority margin for secondary endpoint.

Trial Design and Demographics

  • TANGO was a Phase 3, randomized, multicenter, noninferiority switch study
  • Baseline characteristics were similar between patients receiving DOVATO and TAF-containing regimens, with a median age of 40 and 39, respectively. The majority of patients were male (93% and 91%, respectively) and white (81% and 78%, respectively). The CD4+ T-cell count was ≥500 cells/mm3 in 73% and 80% of the patients in the DOVATO and TAF groups, respectively. Baseline third agent classes in TAF-containing regimens included TAF/FTC plus INSTI (79.6%), NNRTI (12.9%), and PI (7.5%)
  • After a screening period, subjects were randomized to 2 arms: one group was switched to DOVATO (once-daily DTG 50 mg/3TC 300 mg tablet; n=369) while the other continued on TAF-containing regimens (n=372). From Week 148 onward, all patients were switched to DOVATO
  • Week 48 primary endpoint was the proportion of patients with plasma HIV-1 RNA ≥50 copies/mL (by snapshot algorithm, ITT-E, with a 4% noninferiority margin)

Inclusion Criteria

Subjects were included if they met the following criteria:

  • Virologically suppressed adult with HIV-1 RNA <50 copies/mL for >6 months
  • Stable 3- or 4-drug TAF-containing regimen: TAF/FTC + INSTI, NNRTI, or PI as initial regimen
  • No prior virological failure and no documented NRTI or INSTI resistance
  • HBV negative
  • No severe hepatic impairment (Child-Pugh class C)

For your virologically suppressed members with HIV-1

A High Barrier to Resistance With DOVATO at 48 Weeks


*Based on analysis from TANGO through 48 weeks. Confirmed virologic withdrawal was defined as HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA assessment ≥200 copies/mL.
Zero patients in the DOVATO arm had confirmed virologic withdrawal. Therefore, no patients were evaluated for treatment-emergent resistance. One patient on DOVATO, who was withdrawn for protocol deviation (non-compliance with study treatment) and had a last-on-treatment viral load of ≥400 copies/mL, was tested and no INSTI- or NRTI-emergent resistance was detected.

Drug-Related AEs and Discontinuation Rates Through 48 Weeks

*All drug-related AEs are Grade 2 or less.

 

IMPORTANT SAFETY INFORMATION (cont’d)

Contraindications

  • Do not use DOVATO in patients with previous hypersensitivity reaction to dolutegravir or lamivudine
  • Do not use DOVATO in patients receiving dofetilide

For your members with HIV-1 who are either treatment-naïve or virologically suppressed

Update Your Coverage Policy and Formulary for DOVATO Accordingly


*Based on 6 INSTI-based single-tablet regimens for treatment-naïve patients with a WAC price range of $2408.37-$3396.99. IBM ®RED BOOK. Accessed September 1, 2020.

 

IMPORTANT SAFETY INFORMATION (cont’d)

Warnings and precautions

Hypersensitivity Reactions:

  • Hypersensitivity reactions have been reported with dolutegravir and were characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury
  • Discontinue DOVATO immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, as a delay in stopping treatment may result in a life-threatening reaction. Clinical status, including liver aminotransferases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

  • Hepatic adverse events have been reported, including cases of hepatic toxicity (elevated serum liver biochemistries, hepatitis, and acute liver failure), in patients receiving a dolutegravir-containing regimen without pre-existing hepatic disease or other identifiable risk factors
  • Patients with underlying hepatitis B or C or marked elevations in transaminases prior to treatment may be at increased risk for worsening or development of transaminase elevations with use of DOVATO. In some cases, the elevations in transaminases were consistent with immune reconstitution syndrome or hepatitis B reactivation, particularly in the setting where anti-hepatitis therapy was withdrawn
  • Monitoring for hepatotoxicity is recommended

Embryo Fetal Toxicity:

  • Alternative treatments to DOVATO should be considered at the time of conception through the first trimester of pregnancy due to the risk of neural tube defects
  • Perform pregnancy testing before use of DOVATO and counsel that consistent use of effective contraception is recommended while using DOVATO in individuals of childbearing potential

Lactic Acidosis and Severe Hepatomegaly with Steatosis:

Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO and other drugs may occur (see Contraindications and Drug interactions).

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of DOVATO.

Adverse reactions
The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).

Drug interactions

  • Consult full Prescribing Information for DOVATO for more information on potentially significant drug interactions
  • DOVATO is a complete regimen. Coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended
  • Drugs that induce or inhibit CYP3A or UGT1A1 may affect the plasma concentrations of dolutegravir
  • Administer DOVATO 2 hours before or 6 hours after taking polyvalent cation-containing antacids or laxatives, sucralfate, oral supplements containing iron or calcium, or buffered medications. Alternatively, DOVATO and supplements containing calcium or iron can be taken with food

Use in specific populations

  • Pregnancy: There are insufficient human data on the use of DOVATO during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. If planning a pregnancy or if pregnancy is confirmed while taking DOVATO during the first tvrimester, assess the risks and benefits of continuing DOVATO versus switching to another antiretroviral regimen. For individuals actively trying to become pregnant, initiation of DOVATO is not recommended unless there is no suitable alternative
  • Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
  • Females and Males of Reproductive Potential: Perform pregnancy testing before initiation of DOVATO. Advise individuals of childbearing potential to consistently use effective contraception while taking DOVATO
  • Renal Impairment: DOVATO is not recommended for patients with creatinine clearance <50 mL/min
  • Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)

Please see full Prescribing Information, including Boxed Warning, for DOVATO.


3TC=lamivudine; AE=adverse event; ARV=antiretroviral; bATV=boosted atazanavir; bDRV=boosted darunavir; CI=confidence interval; DTG=dolutegravir; EFV=efavirenz; EVG/c=elvitegravir/cobicistat; FTC=emtricitabine; HBV=hepatitis B virus; INSTI=integrase strand transfer inhibitor; ITT-E= intention-to-treat–exposed; NDC=National Drug Code; NNRTI=non-nucleoside reverse transcriptase inhibitor; NPV=nevirapine; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; RAL=raltegravir; RPV=rilpivirine; TAF= tenofovir alafenamide; STR=single-tablet regimen; WAC= wholesale acquisition cost.


Reference:
van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study.

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©2020 ViiV Healthcare or licensor.
DLLOGM200046 October 2020
Produced in USA.